The research proposed in this application deals with the genetic basis of susceptibility to drug-induced cleft palate and other craniofacial anomalies such as micrognathia and agnathia. The primary emphasis is on studying the role of the major histocompatibility complex (H-2 in mice and AgB in rats) in determining susceptibility to these disorders. We propose to localize the specific gene within the mouse H-2 region which is known to affect susceptibility to cortisone-induced cleft palate. We also wish to map precisely the gene which controls the quantity of a cortisol-binding protein, and to determine whether antisera directed to antigens coded by various parts of H-2 can inhibit cortisol binding. The effect of H-2 on sensitivity of thymus cells to corticosteroids will also be studied. We would like to determine whether the same cortisol-binding proteins that are found in fetal palates can be found in or on thymus cells, and whether this explains the H-2-linked differences in thymus cell sensitivity to corticosteroids which have been reported. Other experiments are proposed which will explore the genetic basis of patroclinous inheritance to cleft palate susceptibility, and the possible involvement of the rat AgB locus in drug sensitivities.